With the introduction of glutaraldehyde preservation of biological tissue, and in particular porcine bioprosthetic heart valves, it has become possible to: (a) overcome the poor performance of early formaldehyde-preserved implanted tissue valves; (b) discontinue the use of homograft valves; and (c) avoid the undesirable use of anticoagulants required to prevent thromboembolism associated with the use of non-bioprosthetic (mechanical) heart valves, especially in children. Not unlike other similarly important discoveries, however it appears that the glutaraldehyde-preserved bioprosthesis has created its own dilemma.
Although the relatively biologically inert glutarladehyde-preserved valves of Carpentier and others have demonstrated excellent long-term durability in most instances, serious drawbacks such as tissue-fatigue and a propensity toward calcification have plagued its continued use. Moreover, it was initially contemplated that children and adolescents would be among those deriving the greatest benefit from the glutaraldehyde-preserved bioprosthetic heart valves since the anticoagulants required with mechanical prosthesis could be eliminated. Results from an increasing number of recent clinical studies indicate that severe calcification of these tissues with relatively short-term failure is prevalent among children and adolescents. Thus, despite their long-term durability and overall reduced incidence of complications, these glutarladehyde-preserved valves have been deemed by some to be unsuitable for use in children.
Calcification of tissue remains a mystery for the most part; however, it has previously been shown that various factors including calcium metabolism diseases, age, diet, degeneration of tissue components such as collagen, and turbulance are all involved to a certain extent. Recently, the occurrence of a specific calcium-binding amino acid, laid down after implantation of glutaraldehyde-preserved porcine xenografts, has been demonstrated; and it has been postulated to play a role in calcification. While calcification has been accompanied by degradative changes in the glutaraldehyde-treated collagen fibers of the implanted tissue, it remains unclear whether the dystrophic calcification is a cause or the result of tissue degeneration. Nevertheless, there has been a continued effort to elucidate the source of the calcification problem with implanted tissue, with the hope that a remedy would be soon to follow. Heretofore, neither the source or cause of calcification in biological implants has been ascertained.
It has separately been proposed that calcification of implanted biological tissue can be reduced by treatment thereof with anionic surfactants, and by avoiding contact of the tissue with phosphate ions prior to implantation. These procedures appear promising in view of their effectiveness in reducing calcification of bioprosthetic heart valve tissue. In addition to reducing calcification, the treatment must preserve the durability of the tissue after implantation. In particular, the treatment must maintain the proper hemodynamic properties of the valve and not adversely affect the stiffness of the valve leaflets.
In accordance with the present invention, we have developed a process which effectively reduces calcification of implanted biological tissue, and maintains the proper hemodynamic properties of the valve leaflets in bioprosthetic heart valves. This process advantageously reduces the tendency of bioprosthesis toward calcification and overcomes some of the problems associated with the durability of xenograft heart valves.